1. Field of the Invention
The invention relates to a borosilicate glass having improved hydrolytic resistance for preferred use in the pharmaceutical sector.
2. Description of Related Art
In the pharmaceutical sector, glass is widely used as a packaging material. In particular the special material properties thereof, such as high transparency, mechanical resistance, low permeability in combination with high chemical resistance are decisive for maintaining the quality of medicaments and thus the activity thereof.
The glass containers or primary packaging means for pharmaceutical purposes are generally in direct contact with a medicament present therein and are therefore subject to strict requirements. These are such that the contents can be withdrawn in a suitable manner, wherein at the same time losses as small as possible and no modification, preferably no physical or chemical effects on the contents, occur. The quality of the contents must not be modified by the direct contact with the container or primary packaging means such that the required limiting values are exceeded. In every case it must be ensured that the glass material does not release substances in amounts which could impair the stability of the medicament or even be toxic to the user.
In the case of aqueous-based medicaments, the most important property of a pharmaceutical primary packaging means made of glass is the resistance of the inner surface thereof which comes into contact with the aqueous-based medicament, and is attacked thereby. As a result, diverse ions can be extracted by dissolution from the glass surface. This can lead, for example, in the case of alkali metal and alkaline earth metal ions to a pH shift of the aqueous medium which lowers the activity of the medicament. Of the glass components, in addition, aluminium is suspected of being able to trigger damage to health in people having certain genetic predispositions, e.g. an increased aluminium uptake in metabolism. In order to exclude health risks, therefore, in general as few ions as possible should be extracted from the glass by dissolution.
Frequently used glasses for uses in the pharmaceutical sector are borosilicate glasses, what are termed neutral glasses, or soda lime-silicate glasses. The groups of usable borosilicate glasses is extremely extensive and usually comprises:
SiO2approximately 70 to 80% by weightB2O3approximately 7 to 20% by weightAl2O3approximately 2 to 7% by weightAlkali metal oxideapproximately 3 to 10% by weight.
Numerous glasses of this type have become known from the prior art. For instance, DE 37 22 130 A1 relates to a borosilicate glass which belongs to the first hydrolytic class as specified in DIN 12111, the first acid glass as specified in DIN 12116 and the second alkali glass as specified in DIN 52322, has a linear heat expansion between 20° C. and 300° C. of 4.3 to 5.0×10−6 K−1, a transformation temperature of 535 to 570° C., a processing temperature of 1140 to 1220° C. and a X-ray absorption at 0.6 Å of <5.20 cm−1, and has the following composition:
SiO2 74.5 to 76.5% by weightB2O310.0 to 12.0% by weightAl2O33.5 to 6.0% by weightNa2O 6.0 to 8.0% by weightCaO1.0 to 2.0% by weightZrO20 to 0.50% by weightF0 to 1.0% by weight,wherein As2O3 and/or Sb2O3 and/or NaCl act as fining agents. In order to obtain minimum X-ray absorption, no K2O, BaO or ZnO is present in this borosilicate glass. Some of the borosilicate glasses have relatively low coefficients of thermal expansion α(20° C.; 300° C.) and also relatively high processing temperatures. In addition, the glasses are more susceptible to crystallization because of the missing K2O content.
According to DE 44 30 710 C1, a low boric-acid borosilicate glass of high chemical resistance is disclosed having the following composition in % by weight on an oxide basis:
SiO2>75B2O3 1-<9Al2O33-6Li2O0-4Na2O 0-8K2O0-6MgO0-3CaO0-3BaO0-2SrO0-2ZnO0-3ZrO20-3SnO20-3SnO0-3TiO20-2CeO20-2Fe2O3 0-1, whereSiO2 + B2O3>83   SiO2:B2O3>8  SiO2 + Al2O3 + ZrO2>83   Li2O + Na2O + K2O 5-10MgO + CaO + BaO + SrO + ZnO≦3.  
The boron oxide content of the glass is below the range according to the invention.
DE 100 25 465 C2 describes a low-lithium oxide borosilicate glass which has the following composition (in % by weight on an oxide basis):
SiO272.0-77.0B2O3 5.0-10.0Al2O33.0-7.0ZrO20.1-3.0Li2O 0.05-<0.5  Na2O  0-10.0K2O  0-10.0ZnO  0-8.0CaO  0-5.0BaO  0-5.0SrO  0-5.0TiO2  0-4.0SnO2  0-3.0Fluorides  0-3.0
Fining agents 0-2.0, under the conditions:
Na2O:K2O>0.75SiO2:B2O3>7.5 ΣSiO2 + SnO2 + Al2O3 + ZrO280.0-83.0.
The preferred K2O content is 2.0 to 8.0. All glass compositions cited by way of example have either considerably more or no potassium oxide at all and are therefore not in the range required according to the invention.
In addition, DE 100 27 699 A1 relates to a zirconium oxide- and lithium oxide-containing borosilicate glass of high chemical resistance having the following composition (in % by weight on an oxide basis):
SiO271.5-74.5B2O3 8-11Al2O35-7Li2O  0.1-<0.5Na2O  5-6.5K2O1.8-3  MgO0-1CaO0-2whereMgO + CaO0-2ZrO20.5-2  CeO20-1F   0-0.3,and also optionally usual fining agents in usual amounts.
Thus the K2O content, at 1.8 to 3% by weight, lies outside the range according to the invention and so the effects of the invention cannot be achieved. The alkali metal ion release of this borosilicate glass exhibits excessive values for glass containers in the pharmaceutical sector. In the case of the K2O content cited, furthermore, the rate of evaporation is too high.
According to the disclosure of DE 102 38 915 B3, a borosilicate glass of high hydrolytic resistance is described which has the following composition (in % by weight on an oxide basis):
SiO270.5-<73 B2O3 8-10Al2O3  4-5.6Li2O    0-<0.5Na2O7-9K2O1.2-2.5MgO0-1CaO 0-2, whereMgO + CaO0-2BaO>2-4  ZrO20-2CeO20-1F   0-0.6,and also optionally usual fining agents in usual amounts.
Such a high BaO content of >2-4% by weight cannot be tolerated for primary packaging means in the pharmaceutical sector, in particular if aqueous medicaments are to be present, since sparingly soluble precipitates can form which modify the medicaments and make them unusable in general. Furthermore, these glasses having an aluminium oxide content of 4 to 5.6% by weight are more susceptible to crystallization than the glass composition according to the invention. Therefore, the described borosilicate glasses are not readily processable in a drawing process.
In addition DE 103 37 362 B4 describes an aluminium-free borosilicate glass having good chemical resistance having the following composition (in % by weight on an oxide basis):
SiO260-78B2O3 7-20Li2O 0-2Na2O0-4K2O 3-12MgO0-2CaO 0-2, whereMgO + CaO0-3BaO0-3ZnO0-2ZrO20.8-12 TiO2 0-10CeO20-1F   0-0.6,and also optionally usual fining agents in usual amounts.
This glass composition is aluminium-free and differs fundamentally from the borosilicate glass composition according to the invention.
DE 102 38 930 C1 discloses an aluminium-free borosilicate glass of good chemical resistance having the following composition (in % by weight on an oxide basis):
SiO265.0-77  B2O37.0-20 Li2O 0-2Na2O0-4K2O3.0-12 MgO0-2CaO 0-2, whereMgO + CaO0-3BaO0-3ZnO0-2ZrO20.8-12 TiO20-5CeO20-1F   0-0.6,and also optionally usual fining agents in usual amounts.
This glass composition is aluminium-free and again differs fundamentally from the glass composition according to the invention.
In addition, EP 0 765 847 A1 and also the parallel DE 195 36 708 C1 relates to a zirconium oxide- and lithium oxide-containing borosilicate glass of high chemical resistance and low viscosity having the following composition (in % by weight on an oxide basis):
SiO273.0-75.0B2O3 7.0-10.0Al2O35.0-7.0ZrO21.0-3.0Li2O0.5-1.5Na2O  0-10.0K2O  0-10.0MgO  0-3.0CaO  0-3.0BaO  0-3.0SrO  0-3.0ZnO  0-3.0Fluorides   0-3.0, whereSiO2/B2O3≧7.5ΣSiO2 + Al2O3 + ZrO280.0-83.0ΣMgO + CaO + BaO + SrO + ZnO ≦3.0.
The lithium oxide content exceeds the upper limit according to the invention in such a manner that the advantages of the invention cannot be obtained.
DE 198 42 942 A1 relates to a zirconium oxide- and lithium oxide-containing borosilicate glass of high chemical resistance having the following composition (in % by weight on an oxide basis):
SiO2   71-<73B2O3 7-10Al2O35.5-9 Li2O0.5-2 Na2O   0-10.0K2O    0-10.0, whereLi2O + Na2O + K2O 0.5-10.5MgO 0-2CaO 0-3SrO 0-3BaO 0-3ZnO  0-3, whereMgO + CaO + SrO + BaO + ZnO 0-3ZrO20.8-3 CeO2   0-1,and also optionally usual fining agents in usual amounts.
The lithium oxide content cited exceeds the upper limit according to the invention, and so the advantages according to the invention cannot be obtained.
DE 20 2010 014 985 U1 describes a magnesium oxide containing borosilicate glass which has the following components (in % by weight on an oxide basis):
SiO271.5-78  B2O3 ≧10-12   Al2O3≧3-7   Na2O ≧6.5-8     K2O0.5-2.0MgO1.5-1.9CaO0.3-1.0BaO  0-0.5SrO  0-0.5MgO + CaO + BaO + SrO>2ZrO2 0-1,and also optionally usual fining agents in usual amounts.
This glass composition contains more than 2% by weight of the alkaline earth metal oxides, and so it is unsuitable as primary packaging means in the pharmaceutical sector, in particular for aqueous medicaments, on account of the higher amount of alkaline earth metal oxides.
U.S. Pat. No. 4,386,164 describes a barium-free type I, class B, laboratory glass as specified in ASTM E 438-80a having a linear expansion coefficient (0 to 300° C., cm/cm-° C.×10−7) of about 48 to 56, chemical resistance, a maximum titration equivalent of 0.2N H2SO4/10 g of glass of 1.0 ml, wherein the composition consists substantially of the following components in % by weight:
SiO270-74B2O3  9-13Al2O35-8Na2O 5-8K2O0-4CaO0-3MgO 0-1,wherein the glass composition has an upper cooling temperature of about 550 to 585° C., a softening temperature of about 783 to 799° C., a liquidus temperature of about 1730 to 1760° F. and a log n at the liquidus temperature of about 5.0 to 5.5.
The effects achieved according to the invention are not described. In the exemplary embodiments, only K2O contents of 2.29% by weight and above are cited. Although the comparative composition described has 0.1 to 2.0% K2O, it has a markedly excessive Na2O and CaO+MgO content, which is markedly higher than is allowable according to the invention. In addition, this comparative composition is portrayed as poor with respect to the properties thereof.
U.S. Pat. No. 3,942,992 discloses a chemically resistant glass which is substantially free from alkali metal oxides and B2O3 and exhibits a weight loss of no more than about 0.05 mgs/cm2, when a 5% strength by weight HCl solution is exposed at 95° C. for 24 hours, and a weight loss of no more than about 0.5 mgs/cm2, when a 5% strength by weight NaOH solution is exposed at 95° C. for 6 hours, and substantially consists of (calculated in cation percent on an oxide basis):
SiO259-70%Al2O3 9-15%BaO 5-25%CaO 0-17%ZnO0-7%BaO + CaO + ZnO 15-30%ZrO2   2-<5%.
Although this glass composition is acid- and lye-resistant, the hydrolytic resistance is not mentioned and does not play a role. In addition, the presence of zirconium oxide is obligatory.
The above glasses are not designed especially as pharmaceutical primary packaging means, in particular to be used for medicaments on an aqueous basis. The purpose of the present invention is therefore to find a glass composition having a high resistance to attack by water, that is to say having a low release of ions to an aqueous-based medicament.
The object of the present invention, therefore, is to provide a glass having a glass composition which meets on a high level the requirements of glasses to be used in the pharmaceutical sector, and in particular exhibits a release of ions to an aqueous medium as low as possible, and therefore is preferably suitable for use with aqueous or water-containing medicaments.